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18 F-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard, 68 Ga-labeled SSAs, for somatostatin receptor imaging in patients with neuroendocrine tumors (NETs), given their logistic advantages. Recently, 18 F-AlF-NOTA-octreotide ( 18 F-AlF-OC) has emerged as a promising candidate, but a thorough comparison with 68 Ga-DOTA-SSA in large patient groups is needed. This prospective, multicenter trial aims to demonstrate noninferiority of 18 F-AlF-OC compared with 68 Ga-DOTA-SSA PET in NET patients (ClinicalTrials.gov, NCT04552847). Methods: Seventy-five patients with histologically confirmed NET and routine clinical 68 Ga-DOTATATE ( n = 56) or 68 Ga-DOTANOC ( n = 19) PET, performed within a 3-mo interval of the study scan (median, 7 d; range, -30 to +32 d), were included. Patients underwent a whole-body PET 2 h after intravenous injection of 4 MBq/kg of 18 F-AlF-OC. A randomized, masked consensus read was performed by 2 experienced readers to count tumor lesions. After unmasking, the detection ratio (DR) was determined for each scan, that is, the fraction of lesions detected on a scan compared with the union of lesions of both scans. The differential DR (DDR; difference in DR between 18 F-AlF-OC and 68 Ga-DOTATATE/NOC) per patient was calculated. Tracer uptake was evaluated by comparing SUV max and tumor-to-background ratios in concordant lesions. Results: In total, 4,709 different tumor lesions were detected: 3,454 with 68 Ga-DOTATATE/NOC and 4,278 with 18 F-AlF-OC. The mean DR with 18 F-AlF-OC was significantly higher than with 68 Ga-DOTATATE/NOC (91.1% vs. 75.3%; P < 10 -5 ). The resulting mean DDR was 15.8%, with a lower margin of the 95% CI (95% CI, 9.6%-22.0%) higher than -15%, which is the prespecified boundary for noninferiority. The mean DDRs for the 68 Ga-DOTATATE and 68 Ga-DOTANOC subgroups were 11.8% (95% CI, 4.3-19.3) and 27.5% (95% CI, 17.8-37.1), respectively. The mean DDR for most organs was higher than zero, except for bone lesions (mean DDR, -2.8%; 95% CI, -17.8 to 12.2). No significant differences in mean SUV max were observed ( P = 0.067), but mean tumor-to-background ratio was significantly higher with 18 F-AlF-OC than with 68 Ga-DOTATATE/NOC (31.7 ± 36.5 vs. 25.1 ± 32.7; P = 0.001). Conclusion: 18 F-AlF-OC is noninferior and even superior to 68 Ga-DOTATATE/NOC PET in NET patients. This validates 18 F-AlF-OC as an option for clinical practice somatostatin receptor PET., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Trifluridine/tipiracil showed activity and was well tolerated in a phase 2 study of pretreated patients with advanced gastric cancer done in Japan. We investigated whether the treatment was efficacious compared with placebo in a global population., Methods: TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries. Patients aged 18 years or older with histologically confirmed, non-resectable, metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) as defined by the American Joint Committee on Cancer staging classification (7th edition) who had received at least two previous chemotherapy regimens and had experienced radiological disease progression were eligible for inclusion. Patients were randomly assigned (2:1) via dynamic randomisation from a centralised interactive voice-response system to receive either oral trifluridine/tipiracil (35 mg/m 2 twice daily on days 1-5 and days 8-12 every 28 days) plus best supportive care or placebo plus best supportive care. Participants were allocated to groups by study-site personnel. Randomisation was stratified by region (Japan vs rest of world), ECOG performance status (0 vs 1), and previous treatment with ramucirumab (yes vs no). Both patients and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy was assessed in the intention-to-treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT02500043. The trial, including follow-up of all participants, has been completed., Findings: Between Feb 24, 2016, and Jan 5, 2018, 507 patients were enrolled and randomly assigned, 337 to the trifluridine/tipiracil group and 170 to the placebo group. Median overall survival was 5·7 months (95% CI 4·8-6·2) in the trifluridine/tipiracil group and 3·6 months (3·1-4·1) in the placebo group (hazard ratio 0·69 [95% CI 0·56-0·85]; one-sided p=0·00029, two-sided p=0·00058). Grade 3 or worse adverse events of any cause occurred in 267 (80%) patients in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade 3 or worse adverse events of any cause were neutropenia (n=114 [34%]) and anaemia (n=64 [19%]) in the trifluridine/tipiracil group and abdominal pain (n=15 [9%]) and general deterioration of physical health (n=15 [9%]) in the placebo group. Serious adverse events of any cause were reported in 143 (43%) patients in the trifluridine/tipiracil group and 70 (42%) in the placebo group. One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and because of toxic hepatitis in the placebo group)., Interpretation: Trifluridine/tipiracil significantly improved overall survival compared with placebo and was well tolerated in this heavily pretreated population of patients with advanced gastric cancer. Trifluridine/tipiracil could be a new treatment option in this population who represent a high unmet medical need., Funding: Taiho Oncology and Taiho Pharmaceutical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Purpose: To explore the integration of imaging and molecular data for response prediction to chemoradiotherapy (CRT) for rectal cancer., Material and Methods: Eighty-five rectal cancer patients underwent preoperative CRT. 18 F-FDG PET/CT and diffusion-weighted imaging (DWI) were acquired before (TP1) and during CRT (TP2) and prior to surgery (TP3). Inflammatory cytokines and gene expression were analysed. Tumour response was defined as ypT0-1N0. Multivariate models were built combining the obtained parameters. Final models were calculated on the data combination with the highest AUC., Results: Twenty-two patients (26%) achieved ypT0-1N0 response. 18 F-FDG PET/CT had worse predictive performance than DWI and T2-volumetry (AUC 0.61±0.04, 0.72±0.03, and 0.72±0.02, respectively). Combining all imaging parameters increased the AUC to 0.81±0.03. Adding cytokines or gene expression did not improve the AUC (AUC of 0.72±0.06 and 0.79±0.04 respectively). Final models combining 18 F-FDG PET/CT, DWI, and T2-weighted volumetry at all TPs and using only TP1 and TP3, allowed ypT0-1N0 prediction with a 75% sensitivity, 94% specificity and PPV of 80%., Conclusions: Combining 18 F-FDG PET/CT, DWI, and T2-weighted MRI volumetry obtained before CRT and prior to surgery may help physicians in selecting rectal cancer patients for organ-preservation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer., Methods: The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated., Results: Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS., Conclusions: DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.

Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries., Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method., Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members., Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe., (Copyright © 2013 Elsevier Ltd. All rights reserved.)